| Summary: | While surveying Korean centenarians, I had a fortune to encounter Hansen people, who spent long lives in the restricted sanatorium for leprosy patients. Their unexpectedly long life span compared with the normal population prompted me to examine the background and possible mechanism. Interestingly, a considerable number of these people maintain their intake of 4, 4′-diaminodiphenyl sulfone (DDS), a therapeutic drug for leprosy, habitually for more than three or four decades despite being completely cured of the disease. They have a higher antioxidant activity in their blood than age-matched controls. The protective function of DDS against oxidative stress was confirmed by in vitro tests and in vivo animal models. Moreover, DDS extended life span and increased mobility in a nematode model by inhibiting pyruvate kinase. When DDS effect on functional loss of the older people's muscles was tested, its anti-sarcopenia effect was prominent, especially in non-dominant muscles of DDS-consuming Hansen people. Concerning neurodegenerative disorders, DDS is significantly protective in animal model against Parkinson's disease. Taken together, DDS, serendipitously discovered in the Korean centenarian study, might be a candidate as a new therapeutic modality for protection against aging-dependent dysfunction in neural and muscular degeneration, and possibly for extension of lifespan. Keywords: DDS, Life span, Leprosy, Degeneration, Prevention
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